Use of complement inhibitory proteins to treat spinal cord injury

Abstract

Trauma to the spinal cord initiates an inflammatory response that results in secondary injury to the surrounding tissue, thereby exacerbating the effects of the initial injury. These secondary injury effects are contributed to, in part, by the activation of complement and the associated inflammatory reaction at the site of injury. The present invention describes a method for treating and/or ameliorating these secondary effects and improving locomotor function of a vertebrate that has suffered a spinal cord injury by administering a complement inhibitory protein to the individual as soon as possible after the initial injury occurs. According to this method, by inhibiting the activation of complement, inflammation and the resulting secondary tissue injury are reduced, thereby improving the prognosis of a patient suffering a spinal cord injury.

1 . A method for treating a spinal cord injury in a vertebrate subject comprising: 
 administering a complement inhibitory protein to said vertebrate as soon as possible after said injury.    
     
     
         2 . The method according to  claim 1 , wherein said complement inhibitory protein is selected from the group consisting of: complement receptor type I (CR1), factor H, C4-binding protein (C4-BP), membrane cofactor protein (MCP), decay accelerating factor (DAF), fragments thereof that retain complement inhibiting properties, complement-inhibiting antibodies, and sCR1-sLe x .  
     
     
         3 . The method according to  claim 2 , wherein said vertebrate is a human.  
     
     
         4 . The method according to  claim 2 , wherein said complement inhibitory protein is a soluble CR1 protein.  
     
     
         5 . The method according to  claim 4 , wherein said soluble CR1 is a polypeptide comprising at least the N-terminal two short consensus repeats of full-length human CR1.  
     
     
         6 . The method according to  claim 5 , wherein said soluble CR1 is a polypeptide comprising the extracellular domain of mature human CR1.  
     
     
         7 . The method according to  claim 4 , wherein said soluble CR1 has the amino acid sequence of SEQ ID NO:3.  
     
     
         8 . A method for improving the locomotor function of a vertebrate subject suffering from a spinal cord injury comprising: administering a complement inhibitory protein to said subject as soon as possible after said injury.  
     
     
         9 . The method according to  claim 8 , wherein said complement inhibitory protein is selected from the group consisting of: complement receptor type I (CR1), factor H, C4-binding protein (C4-BP), membrane cofactor protein (MCP), decay accelerating factor (DAF), fragments thereof that retain complement inhibiting properties, complement-inhibiting antibodies, and sCR1-sLe x .  
     
     
         10 . The method according to  claim 9 , wherein said vertebrate is a human.  
     
     
         11 . The method according to  claim 9 , wherein said complement inhibitory protein is a soluble CR1 protein.  
     
     
         12 . The method according to  claim 11 , wherein said soluble CR1 is a polypeptide comprising at least the N-terminal two short consensus repeats of full-length human CR1.  
     
     
         13 . The method according to  claim 12 , wherein said soluble CR1 is a polypeptide comprising the extracellular domain of mature human CR1.  
     
     
         14 . The method according to  claim 11 , wherein said soluble CR1 has the amino acid sequence of SEQ ID NO:3.  
     
     
         15 . A pharmaceutical composition for use in treating a spinal cord injury comprising a therapeutically effective amount of a soluble CR1 protein and a pharmaceutically acceptable excipient or carrier.  
     
     
         16 . The pharmaceutical composition according to  claim 15 , wherein the soluble CR1 protein is a polypeptide comprising the extracellular domain of mature human CR1.  
     
     
         17 . The pharmaceutical composition according to  claim 15 , wherein the soluble CR1 protein is a polypeptide having the amino acid sequence of SEQ ID NO:3.